The dorsal horn of the spinal cord is an important site of afferent sensory transmission to central neurons. Interactions between the synaptic receptors and voltage-gated calcium channels (VGCCs), and their combined effects on Ca2+ entry, have not been well studied in dorsal horn neurons or elsewhere in the central nervous system. Yet the physiological effects of [Ca2+]i and calcium-driven changes in membrane potentials could have profound influence on the sensation of peripheral stimuli in both normal and pathological states. Fast synaptic transmission between primary afferents and their dorsal horn targets primarily involves an excitatory transmitter, glutamate, acting on one or more of a family of synaptic excitatory amino acid (EAA) receptors known as the NMDA, and non-NMDA or kainate and quisqualate receptors. EAAs will depolarize the cells by activation of these receptors and indirectly activate VGCCs causing [Ca2+]i to elevate and membrane potential to become more depolarized. This form of interaction implies synaptic activation of Ca2+-dependent potentials with highly nonlinear boosting of both the change in membrane potential and [Ca2+]i. Recent experiments have also suggested that kainate-activated receptor operated channels (ROCs) permeable to Ca2+ exist. If these are in dorsal horn neurons, it could completely change the localization, kinetics and voltage dependence of Ca2+ entry during synaptic activation. Finally, the possibility of a non-NMDA receptor that is metabolically coupled having a role in synaptic transmission in dorsal horn neurons is untested. Therefore, the regulation of Ca2+ entry will be studied following non-NMDA receptor activation to determine 1) if Ca2+ entry through the non-NMDA receptors occurs, 2) the contribution of VGCC properties to determining the amplitude and time course of the evoked [Ca2+]i transient and 3) the role of Ca2+ release in non-NMDA receptor mediated changes in [Ca2+]i. Simultaneous measurement of [Ca2+]i and membrane potential changes should be particularly informative about whether Ca2+ entry is due to Ca2+- dependent action potentials or sustained opening of VGCCs. Dendritic receptor and channel properties will be studied using low light level video imaging for good spatial resolution and photomultiplier tubes for good time resolution. Such studies will improve our understanding of the complex interactions that normally occur among synaptic inputs and VGCCs in the dorsal horn. Furthermore changes in [Ca2+]i have been implicated in processes of activity dependent facilitation of synaptic transmission such as might underlie pathological pain syndromes like allodynia. Finally, since sustained EAA-mediated elevation of [Ca2+]i in spinal cord neurons is associated with secondary cell death following traumatic spinal cord injury, these experiments may improve the basic understanding of the mechanisms associated with cell death.